Abstract
Context
Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated.
Case report
A 46-year-old ...woman presented with abdominal pain, hypotension, and skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 µg/dL, adrenocorticotropin (ACTH) of 807 pg/mL, and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone.
Discussion
We identified 9 articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in 5 cases, but ACTH levels were measured in only 3 cases (high in 1 case and normal/low in other 2 cases). Bilateral adrenal nonhemorrhagic or hemorrhagic infarction was identified in 5 reports (2 had adrenal insufficiency, 2 had normal cortisol levels, and 1 case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19.
Conclusion
Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.
Abstract
Context
Primary aldosteronism (PA) is the most common cause of endocrine hypertension (HT). HT remission (defined as blood pressure <140/90 mm Hg without antihypertensive drugs) has been ...reported in approximately 50% of patients with unilateral PA after adrenalectomy. HT duration and severity are predictors of blood pressure response, but the prognostic role of somatic KCNJ5 mutations is unclear.
Objective
To determine clinical and molecular features associated with HT remission after adrenalectomy in patients with unilateral PA.
Methods
We retrospectively evaluated 100 patients with PA (60 women; median age at diagnosis 48 years with a median follow-up of 26 months). Anatomopathological analysis revealed 90 aldosterone-producing adenomas, 1 carcinoma, and 9 unilateral adrenal hyperplasias. All patients had biochemical cure after unilateral adrenalectomy. KCNJ5 gene was sequenced in 76 cases.
Results
KCNJ5 mutations were identified in 33 of 76 (43.4%) tumors: p.Gly151Arg (n = 17), p.Leu168Arg (n = 15), and p.Glu145Gln (n = 1). HT remission was reported in 37 of 100 (37%) patients. Among patients with HT remission, 73% were women (P = 0.04), 48.6% used more than three antihypertensive medications (P = 0.0001), and 64.9% had HT duration <10 years (P = 0.0015) compared with those without HT remission. Somatic KCNJ5 mutations were associated with female sex (P = 0.004), larger nodules (P = 0.001), and HT remission (P = 0.0001). In multivariate analysis, only a somatic KCNJ5 mutation was an independent predictor of HT remission after adrenalectomy (P = 0.004).
Conclusion
The presence of a KCNJ5 somatic mutation is an independent predictor of HT remission after unilateral adrenalectomy in patients with unilateral PA.
The impact of KCNJ5 somatic mutations on hypertension remission after adrenalectomy brings new insight into the postoperative follow-up of patients with PA.
Abstract
Context
Primary aldosteronism (PA) screening relies on an elevated aldosterone to renin ratio with a minimum aldosterone level, which varies from 10 to 15 ng/dL (277-415.5 pmol/L) using ...immunoassay.
Objective
To evaluate intra-individual coefficient of variation (CV) of aldosterone and aldosterone to direct renin concentration ratio (A/DRC) and its impact on PA screening.
Methods
A total of 671 aldosterone and DRC measurements were performed by the same chemiluminescence assays in a large cohort of 216 patients with confirmed PA and at least 2 screenings.
Results
The median intra-individual CV of aldosterone and A/DRC was 26.8% and 26.7%. Almost 40% of the patients had at least one aldosterone level <15 ng/dL, 19.9% had at least 2 aldosterone levels <15 ng/dL, and 16.2% had mean aldosterone levels <15 ng/dL. A lower cutoff of 10 ng/dL was associated with false negative rates for PA screening of 14.3% for a single aldosterone measurement, 4.6% for 2 aldosterone measurements, and only 2.3% for mean aldosterone levels. Considering the minimum aldosterone, true positive rate of aldosterone thresholds was 85.7% for 10 ng/dL and 61.6% for 15 ng/dL. An A/DRC >2 ng/dL/µIU/mL had a true positive rate for PA diagnosis of 94.4% and 98.4% when based on 1 or 2 assessments, respectively. CV of aldosterone and A/DRC were not affected by sex, use of interfering antihypertensive medications, PA lateralization, hypokalemia, age, and number of hormone measurements.
Conclusion
Aldosterone concentrations had a high CV in PA patients, which results in an elevated rate of false negatives in a single screening for PA. Therefore, PA screening should be based on at least 2 screenings with concomitant aldosterone and renin measurements.
Few studies demonstrated a percentage decrease in the estimated glomerular filtration rate (eGFR) at a single time and the rate of hypoaldosteronism after adrenalectomy for primary aldosteronism ...(PA). Our aim was to investigate the evolution of renal function and the hypoaldosteronism risk after adrenalectomy for PA. Aldosterone, renin, eGFR, and electrolyte levels were determined before and at 1 week, 1, 3 and 6 months after unilateral adrenalectomy in 94 PA patients (40 men and 54 women). The main outcome was the postoperative eGFR decline using analysis of covariance with the preoperative eGFR as a covariate. eGFR decreased during first postoperative week compared to 3 months before surgery. During the first 6 months, eGFR remained stable at similar levels to the first week after surgery. Age (p=0.001), aldosterone levels (p=0.021) and eGFR 3 months before surgery (p+<+0.0001) had a significant correlation with eGFR during first postoperative week. High aldosterone levels at diagnosis were correlated with decline in renal function in the univariate model (p=0.033). In the multivariate analysis, aldosterone levels at diagnosis had a tendency to be an independent predictor of renal function after surgery (p=0.059). Postoperative biochemical hypoaldosteronism was diagnosed in 48% of the cases after adrenalectomy, but prolonged hyperkalemia occurred in only 4 cases (4.5%). Our findings showed a decrease of eGFR after unilateral adrenalectomy for PA. Additionally, aldosterone levels at diagnosis correlated with postoperative renal function. Postoperative biochemical hypoaldosteronism occurred in almost half of the patients, but prolonged hyperkalemia with fludrocortisone replacement was less frequent.
Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved.
To evaluate the ...efficacy of oral furosemide as a new confirmatory test for PA diagnosis.
We prospectively evaluated the diagnostic performance of 80 mg of oral furosemide in 64 patients with PA and 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, and 2 hours and 3 hours after the oral furosemide. In addition, the oral furosemide test was compared with 2 other confirmatory tests: the furosemide upright test (FUT) and saline infusion test (SIT) or captopril challenge test (CCT) in all patients with PA.
The cut-off of 7.6 µU/mL for DRC at 2 hours after oral furosemide had a sensitivity of 92%, specificity of 82%, and accuracy of 90% for PA diagnosis. In 5 out of 6 controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these 6 controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2 hours after oral furosemide had a sensitivity of 95.3%, specificity of 93.7% and accuracy of 95% for PA diagnosis. DRC after 3 hours of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) patients with PA. Only 4 out of 64 cases with PA (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any patient with PA during the test.
The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.
Abstract
Disclosure: T. Castanheira de Freitas: None. A.W. Maciel: None. G.F. Fagundes: None. J. Petenuci: None. L. Santana: None. A. Guimaraes: None. F. Freitas-Castro: None. V. Srougi: None. F. ...Tanno: None. J. Chambo: None. M. Pereira: None. F. Coelho: None. L.P. Brito: None. A. Cavalcante: None. B. Pilan: None. F. Carnevale: None. A. Pio-Abreu: None. L. Bortolotto: None. A. Latronico: None. M.C. Fragoso: None. L. Drager: None. B.B. Mendonca: None. M.Q. Almeida: None.
Background: Confirmatory tests represent a fundamental step in primary aldosteronism (PA) diagnosis, but they are laborious and often require a hospital environment due to the risks involved. The most common tests are the saline infusion test (SIT), captopril chalenging test (CCT), fludrocortisone supression test (FST) and furosemide upright test (FUT). The sodium overloading tests are the most frequently used tests in clinical practice, but are not tolerated in patients with severe hypertension, hypervolemia and hypokalemia. The use of oral furosemide test as a new confirmatory test to simplify the confirmation of PA diagnosis was not investigated. Methods: We prospectively evaluated the diagnostic performance of oral 80 mg furosemide in 64 PA patients and in 22 with primary hypertension (controls). Direct renin concentration (DRC) was measured before, 2h and 3h after the oral furosemide. In addition, the oral furosemide test was compared with two other confirmatory tests: FUT and SIT or CCT in all PA patients. Results: The cut-off of 7.6 µU/mL for DRC at 2h after oral furosemide had a sensitivity of 92%, a specificity of 82% and an accuracy of 90% for PA diagnosis. The cut-off of 10 µU/mL at 2h had a higher sensitivity of 95.3%, but a lower specificity of 73%. In five out of six controls with low-renin hypertension, which might represent a PA spectrum, renin remained suppressed. Excluding these six controls with low-renin hypertension, the DRC cut-off of 10 µU/mL at 2h after oral furosemide had a sensitivity of 95.3%, a specificity of 93.7% and an accuracy of 95% for PA diagnosis. DRC after 3h of oral furosemide did not improve diagnostic performance. Using the cut-off of 10 µU/mL, the oral furosemide test and the FUT were concordant in 62 out of 64 (97%) PA patients. Only 4 out of 64 PA cases (6.4%) ended the oral furosemide test with potassium <3.5 mEq/L. Hypotension was not evidenced in any PA patient during the test. Conclusion: The oral furosemide test was safe, well-tolerated and represents an effective strategy for PA investigation.Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6 (to M.Q. Almeida) and by the Coordination of Superior Level Staff Improvement (CAPES) fellowship (to TCF).
Presentation: Friday, June 16, 2023
Abstract
Disclosure: M.A. Stumpf: None. N.L. Queiroz: None. V.C. Souza: None. A.W. Maciel: None. G.F. Fagundes: None. V. Srougi: None. F.Y. Tanno: None. J.L. Chambo: None. M.A. Pereira: None. A. ...Pio-Abreu: None. L.A. Bortolotto: None. A. Latronico: None. M.B. Fragoso: None. L.F. Drager: None. B.B. Mendonca: None. M.Q. Almeida: None.
Background: Primary aldosteronism (PA) is a very prevalent disease, characterized by an autonomous aldosterone secretion. Unilateral PA accounts for approximately 40% of the cases and is preferentially treated with surgery. Several studies reported decrease in renal function following unilateral adrenalectomy, but the risk factors associated with this decline remain to be better elucidated. Aim: Our aim was to investigate predictive factors of the decrease in renal function after unilateral adrenalectomy for PA. Methods: We retrospectively evaluated 89 PA patients submitted to unilateral adrenalectomy. Serum aldosterone, direct renin concentration, estimated glomerular filtration rate (eGFR), and electrolytes were determined at the pre-operative period and at 1 week, 1, 3 and 6 months (m) after unilateral adrenalectomy. The primary endpoint was the DELTAeGFR (eGFR after surgery at different times – eGFR before surgery). Results: Thirty-seven patients (41.6%) were men and 52 (58.4%) were women, with a median age of diagnosis of 49 years (range, 20 to 74 years). At diagnosis, the median aldosterone and renin levels were 29.8 ng/dl (7.3 - 217) and 4 μIU/mL (4 – 8.2), respectively. Hypokalemia at diagnosis was evidenced in 75 out of 89 (84.3%) of the patients. Unilateral PA was confirmed in 78 out of 89 cases (87.6%) by biochemical cure after adrenalectomy. The mean pre-operative creatinine and eGFR were 1.14 ± 0.48 mg/dL and 53.5 ± 17.1 mL/min, respectively. After adrenalectomy, the DELTAeGFR was −6.7 ± 12.1 mL/min at 1 week (p= 0.001), 0.17 ± 10 mL/min at 1m (p= 0.91), −2 ± 8.7 mL/min at 3m (p= 0.13) and −1.8 ± 10.9 mL/min at 6m (p= 0.24). Interestingly, aldosterone levels at diagnosis were significantly associated with the DELTAeGFR at 1 week (p= 0.024). PA patients with aldosterone levels >50 ng/dL (n= 13) at diagnosis presented a higher deterioration in renal function at 1 week when compared to those with aldosterone <50 ng/dL (n= 76) (αeGFR −12 ± 8.6 mL/min vs. −5.9 ± 12.5 mL/min, respectively; p= 0.032). Moreover, the patients with hypoaldosteronism (aldosterone <5 ng/dl) at 1 week had a lower decrease in renal function (DELTAeGFR −4.4 ± 12mL/min (n= 41) vs. −9.9 ± 11.6 mL/min (n= 42), respectively; p= 0.014) and lower levels of aldosterone at diagnosis (31.5 ± 21.1 ng/dL vs. 50.4 ± 44.4 ng/dL, respectively; p= 0.008). The post-operative decline in renal function did not correlate with age, hypokalemia, number of anti-hypertensive medications at diagnosis, immediate pre-operative and post-operative renin, and hypertension remission after surgery. Conclusion: The renal function decreased precociously after adrenalectomy but returned to basal levels after 1m. Aldosterone levels at diagnosis and at 1 week after surgery were significantly associated with decline in renal function. Support: This work was supported by the Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6.
Presentation: Friday, June 16, 2023
Coronavirus disease 2019 (COVID-19) is a proinflammatory and prothrombotic condition, but its impact on adrenal function has not been adequately evaluated.
A 46-year-old woman presented with ...abdominal pain, hypotension, skin hyperpigmentation after COVID-19 infection. The patient had hyponatremia, serum cortisol <1.0 ug/dL, ACTH of 807 pg/mL and aldosterone <3 ng/dL. Computed tomography (CT) findings of adrenal enlargement with no parenchymal and minimal peripheral capsular enhancement after contrast were consistent with bilateral adrenal infarction. The patient had autoimmune hepatitis and positive antiphospholipid antibodies, but no previous thrombotic events. The patient was treated with intravenous hydrocortisone, followed by oral hydrocortisone and fludrocortisone.
Among 115 articles, we identified nine articles, including case reports, of new-onset adrenal insufficiency and/or adrenal hemorrhage/infarction on CT in COVID-19. Adrenal insufficiency was hormonally diagnosed in five cases, but ACTH levels were measured in only three cases (high in one case and normal/low in other two cases). Bilateral adrenal non- or hemorrhagic infarction was identified in five reports (two had adrenal insufficiency, two had normal cortisol levels and one case had no data). Interestingly, the only case with well-characterized new-onset acute primary adrenal insufficiency after COVID-19 had a previous diagnosis of antiphospholipid syndrome. In our case, antiphospholipid syndrome diagnosis was established only after the adrenal infarction triggered by COVID-19.
Our findings support the association between bilateral adrenal infarction and antiphospholipid syndrome triggered by COVID-19. Therefore, patients with positive antiphospholipid antibodies should be closely monitored for symptoms or signs of acute adrenal insufficiency during COVID-19.
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